Cellulose powder

ABSTRACT

This cellulose powder has: an average degree of polymerization of 100 to 350; a weight average particle size of over 30 μm, but less than 250 μm; an apparent specific volume of 2 to less than 15 cm 3 /g; and an organic carbon content from residual impurities, which is defined by the total organic carbon content (%) during 1% NaOH extraction to the total organic carbon content (%) during pure water extraction, of over 0.07 to 0.3%.

TECHNICAL FIELD

The present invention relates to a cellulose powder used inpharmaceutical, food, and industrial applications. More specifically,the present invention relates to a cellulose having improved compressioncompactibility and high effects of improving flavor release from Kampomedicines or the like and coloring of sugar coated tablets or the like,and suitable for excipients for compression and granulation inapplications of pharmaceuticals. The present invention also relates tomolded articles comprising the cellulose.

BACKGROUND ART

Kampo medicines have been positively taken for improvement in health andprevention of disease in recent years. The unique bad odors of Kampomedicines cause difficulties and obstacles to the intake thereof.

Tablets containing Kampo medicines having bad odors have been coatedwith sugar to suppress the odors, or have been compounded withsweeteners to mask their bitterness.

Sweeteners, if compounded, undesirably increase the calories of Kampomedicines to be taken for prevention and improvements of diabetes,obesity, and the like. For this reason, methods of improving bad odorsof Kampo medicines without compounding sweeteners have been required.The content per tablet of Kampo medicines is large, and a number ofKampo medicines are raw powders having large specific volumes. Suchbulkiness limits the amount of an excipient for compression to becompounded, and as a result, tablets are readily worn. For this reason,an excipient for compression having high compression compactibility hasbeen required.

Patent Literature 1 describes a formulation that can reduce the badtaste unique to Bofutsushosan by compounding a microcrystallinecellulose.

As an excipient to enhance compactibility, microcrystalline cellulosesdescribed in Patent Literatures 2 to 5 are known.

CITATION LIST Patent Literature

-   Patent Literature 1: JP 2009-242328 A-   Patent Literature 2: JP 40-26274 B-   Patent Literature 3: JP 56-2047 B-   Patent Literature 4: International Publication No. WO2006/115198-   Patent Literature 5: JP 57-212231 A

SUMMARY OF INVENTION Technical Problem

Unfortunately, the formulation described in Patent Literature 1 containsthe microcrystalline cellulose described in Patent Literature 3, whichis prepared by a method different from the method according to thepresent invention. The microcrystalline cellulose may have poorcompactibility when the contents of main drugs are larger. As a result,satisfactory tablets cannot be always obtained. The formulation stillhas the odors of Kampo medicines. The formulations as sugar coatedtablets undesirably reduce the whiteness of sugar coating layers. PatentLiterature 2 describes a microcrystalline cellulose having an averagedegree of polymerization of 15 to 375, an apparent specific volume of1.84 to 8.92 cm³/g, a particle size of 300 μm or less. Patent Literature3 describes a microcrystalline cellulose having an average degree ofpolymerization of 60 to 375, an apparent specific volume of 1.6 to 3.1cm³/g, an apparent dense specific volume of 1.40 cm³/g or more, 2 to 80%by weight particles of 200 mesh or more, and an angle of repose of 35 to42°. Patent Literature 4 describes a porous cellulose aggregate having asecondary aggregation structure formed by aggregation of celluloseprimary particles, having an intraparticle pore volume of 0.265 cm³/g to2.625 cm³/g, containing I-type crystals, having an average particle sizeof more than 30 μm and 250 μm or less, a specific surface area of 0.1m²/g or more and less than 20 m²/g, an angle of repose of 25° or moreand less than 44°, a degree of swelling of 5% or more, anddisintegration properties in water. Patent Literature 5 describes amethod of preparing a cellulose powder in which a cellulose raw materialcomposed of cellulose fibers having a diameter of 2 to 2.0 μm ishydrolyzed with mineral acid to prepare a depolymerized product havingan average degree of polymerization of about 100 to 300, and thedepolymerized product is cut into a specific shape in a liquid until theresulting product reaches the size so as to pass through a metallic meshof about 60 mesh. These microcrystalline celluloses, which haveconfigurations different from that of the cellulose powder according tothe present invention, have poor compactibility, attain insufficientflavor release from Kampo medicines used in combination, or may reducethe whiteness of sugar coating layers in formation of sugar coatedtablets.

An object of the present invention is to provide a cellulose powderhaving high compression compactibility, and improving flavor releasefrom Kampo medicines or the like and coloring properties of sugarcoating layers of sugar coated tablets.

Solution to Problem

The present inventors, who have conducted extensive research inconsideration of such circumstances, have found that a cellulose powderhaving physical properties controlled to fall within specific ranges canimprove not only compression compactibility but also flavor release fromKampo medicines or the like and coloring properties of sugar coatinglayers, and have achieved the present invention. Namely, the presentinvention is as follows.

(1) A cellulose powder having an average degree of polymerization of 100to 350, a weight average particle size of more than 30 μm and 250 μm orless, an apparent specific volume of 2 to 15 cm³/g, and an amount oforganic carbon derived from residual impurities of more than 0.07 and0.3% or less, the amount of organic carbon derived from residualimpurities being defined by the expression: amount of total organiccarbon (%) during extraction with 1% NaOH−amount of total organic carbon(%) during extraction with pure water.(2) The cellulose powder according to (1), wherein the apparent specificvolume is 2 to 6 cm³/g.(3) The cellulose powder according to (1), wherein the apparent specificvolume is 2 cm³/g or more and less than 4 cm³/g.(4) The cellulose powder according to any one of (1) to (3), wherein anintraparticle pore volume is 0.1 cm³/g or more and less than 0.265cm³/g.(5) The cellulose powder according to (1), wherein a water absorptioncapacity is 1.8 to 4.0 cm³/g.(6) A molded article comprising the cellulose powder according to anyone of (1) to (5).(7) The molded article according to (6), wherein the molded article is atablet containing one or more active ingredients.(8) A method of preparing a cellulose powder, comprising: hydrolyzing anatural cellulose substance at a hydrochloric acid concentration of 0.05to 0.3% at a hydrolysis temperature of 80 to 150° C. for a hydrolysistime of 40 to 150 minutes to control a volume average particle size ofparticles in a cellulose dispersion liquid after the hydrolysis to be 70to 200 μm, and then spray drying the resulting dispersion liquid toprepare a cellulose powder having an average degree of polymerization of100 to 350, a weight average particle size of more than 30 μm and 250 μmor less, an apparent specific volume of 2 to 15 cm³/g, and an amount oforganic carbon derived from residual impurities of more than 0.07 and0.3% or less, the amount of organic carbon derived from residualimpurities being defined by the expression: amount of total organiccarbon (%) during extraction with 1% NaOH−amount of total organic carbon(%) during extraction with pure water.(9) A molded article including one or more active ingredients, one ormore additives selected from saccharides, sugar alcohols, starches, anddisintegrating agents, and a cellulose powder, wherein the moldedarticle has a hardness of 50 to 200 N, a tensile strength of 0.1 to 12MPa, a friability of 0 to 0.5%, a swelling rate of a diameter of themolded article in acetone of 0 to 3.3% or less.(10) The molded article according to (9), comprising 5 to 90% by weightof a cellulose powder.(11) The molded article according to (9) or (10), wherein an amount oftotal organic carbon derived from residual impurities according tomolded article residues obtained through washing of the molded articlewith acetone, ethanol, pure water, and ethanol sequentially andextraction is more than 0.07 and 0.3% or less.(12) The molded article according to (9) or (10), wherein the amount oftotal organic carbon derived from residual impurities in the cellulosepowder obtained through washing of the molded article with acetone,ethanol, pure water, and ethanol sequentially and extraction is morethan 0.07 and is 0.3%.

Advantageous Effects of Invention

The cellulose powder according to the present invention has highcompression compactibility and can improve flavor release from Kampomedicines or the like and the coloring properties of sugar coatinglayers of sugar coated tablets.

BRIEF DESCRIPTION OF DRAWING

FIG. 1 is a diagram showing the relationship between the apparentspecific volume and the hardness of the cellulose powder according tothe present invention (Examples 1 to 4) and the conventional cellulosepowder (Comparative Examples 1 and 2).

DESCRIPTION OF EMBODIMENTS

The present invention will now be described in more detail.

The cellulose powder according to the present invention has an averagedegree of polymerization of 100 to 350, preferably 150 to 300, morepreferably 180 to 250. The average degree of polymerization of 100 ormore is preferred because the compactibility is improved, and theaverage degree of polymerization of 350 or less is preferred because thepowder has high fluidity and disintegration properties while fibrousproperties are not demonstrated. Namely, an average degree ofpolymerization of 100 to 350 is preferred because it attainsparticularly well-balanced compactibility, disintegration properties,and fluidity.

The cellulose powder according to the present invention should have aweight average particle size of more than 30 μm and 250 μm or less. Aweight average particle size of more than 30 μm improves handlingwithout increasing adhering and aggregating properties, and attains highfluidity. A weight average particle size of 250 μm or less is preferredbecause such a size does not separate or segregate the cellulose powderfrom the active ingredient, and may not reduce the content uniformity offormulations. The weight average particle size is preferably more than30 μm and 180 μm or less.

The cellulose powder according to the present invention should have anapparent specific volume of 2 to 15 cm³/g. The apparent specific volumeis preferably 2 to 13 cm³/g, more preferably 2 to 6 cm³/g, particularlypreferably 2 cm³/g or more and less than 4 cm³/g. An apparent specificvolume of 2 cm³/g or more improves compactibility. The upper limit is atmost 15 cm³/g because an apparent specific volume more than the upperlimit restores elasticity due to fibrous properties. The upper limit ispreferably 6 cm³/g or less, more preferably less than 4 cm³/g becausefluidity and disintegration properties are improved. The apparentspecific volume is preferably 2.3 to 3.8 cm³/g, particularly preferably3.0 to 3.8 cm³/g.

The cellulose powder according to the present invention preferably hasan apparent tapping density of 0.2 to 0.6 g/cm³. The apparent tappingdensity is more preferably 0.3 to 0.58 g/cm³, particularly preferably0.35 to 0.55 g/cm³. When an apparent tapping density is 0.6 g/cm³ orless, compactibility is improved.

The cellulose powder according to the present invention preferably hasan angle of repose of 36° or more and less than 44° as an index offluidity of the powder from the viewpoint of the content uniformity. Theangle of repose is more preferably 38° to 42°.

The cellulose powder according to the present invention preferably hasan intraparticle pore volume of substantially zero. The value of theintraparticle pore volume determined by the method according toWO2006/115198 is preferably 0.1 cm³/g or more and less than 0.265 cm³/g.If the particles have substantially no inner pores, flavor release canbe improved without adsorbing even flavors with good smells, and thusthis is preferable.

The cellulose powder according to the present invention should have anamount of organic carbon derived from impurities remaining in thecellulose raw material of more than 0.07 and 0.3% or less. The amount ispreferably more than 0.07 and 0.25%, more preferably 0.09 to 0.15%. Inthe present invention, the amount of organic carbon derived fromresidual impurities is defined by the difference (%) between the amountof total organic carbon (TOC) in 5 g of a cellulose powder extractedfrom the cellulose powder (5 g) with pure water (80 mL) and the amountof TOC in 5 g of a cellulose powder extracted from the cellulose powder(5 g) with an aqueous solution of 1% sodium hydroxide (80 mL). Theamount of TOC extracted with the aqueous solution of 1% sodium hydroxidereflects the amounts of an alkali-soluble ingredient and a purewater-soluble ingredient contained in the cellulose powder. From theamount of TOC, the amount of TOC extracted with pure water, namely, thepure water-soluble ingredient is subtracted to determine the amount ofthe alkali-soluble ingredient in the cellulose powder. The value iscorrelated with the amount of organic carbon derived from residualimpurities.

In the cellulose powder according to the present invention, the amountof organic carbon derived from residual impurities, which is defined inthe present invention, is higher than that of the cellulose powderprepared by a conventional method. The organic carbon derived fromresidual impurities is an alkali-soluble ingredient slightly containedin the cellulose powder. Surprisingly, the present inventors have foundthat a larger amount of organic carbon derived from residual impuritiesleads to higher compression compactibility. The organic carbon derivedfrom residual impurities, although slightly contained, is present on thesurfaces of individual cellulose powder particles to enhance theadhesive force. If the amount of organic carbon derived from residualimpurities is controlled to fall within the range specified in thepresent invention, compactibility is improved by 10 to 300%. The presentinventors have also found that the ingredient slightly contained cancontribute to an improvement in flavor release. This is probably becausethe organic carbon derived from residual impurities as defined in thepresent invention adsorbs ingredients having strong odors to increasethe concentrations of flavors with good smells probably contained innatural products, and thus improves bad odors of ingredients.Furthermore, the present inventors have found that the organic carbonderived from residual impurities has emulsifying properties, whichimproves dispersibility in sugar. For this reason, when the cellulosepowder is added to the sugar coating layer, the cellulose powder isentirely dispersed to enhance the coloring properties of the sugarcoating layer.

If the amount of organic carbon derived from residual impurities iscontrolled within the range specified in the present invention,compression compactibility and improvements in flavor release andcoloring properties of sugar coating layers can be demonstrated in agood balance.

The cellulose powder according to the present invention is prepared byhydrolyzing a natural cellulose substance under a condition where theacid concentration is lower than that in the conventional method.Namely, a natural cellulose substance is hydrolyzed at a hydrochloricacid concentration of 0.05 to 0.3% at a reaction temperature of 80 to150° C. for 40 to 150 minutes after the temperature reaches thepredetermined reaction temperature. Thereby, impurities inside celluloseparticles correlated with the amount of organic carbon derived fromresidual impurities extracted from cellulose particles with hot waterduring the hydrolysis can be reduced. After drying, the amount oforganic carbon derived from residual impurities can be increased insidethe cellulose particles. As a result, the flavor release effect is alsoimproved. A concentration of hydrochloric acid of 0.05% or more ispreferred because the amount of organic carbon derived from residualimpurities inside the cellulose particles after drying is notsignificantly increased, and compression compactibility anddisintegration properties in water are well balanced. The flavor releaseeffect is also likely to be improved. A concentration of hydrochloricacid of 0.3% or less is preferred because the amount of organic carbonderived from residual impurities inside the cellulose particles afterdrying is increased, and the effects of improving flavor release, thecoloring properties of sugar coating layers, and the like according tothe present invention are attained. A preferred range of theconcentration of hydrochloric acid is 0.08 to 0.25%, particularlypreferably 0.08 to 0.15%. A preferred range of the reaction temperatureis 100 to 150° C., and a preferred range of the reaction time is 70 to110 minutes.

Stirring should be performed under the hydrolysis condition to controlthe volume average particle size of particles in the cellulosedispersion liquid after the hydrolysis to be 70 to 200 μm. Preferably,the volume average particle size of particles in the cellulosedispersion liquid after hydrolysis is 70 to 150 μm. Preferably, afterdehydration of the cellulose dispersion liquid, the product is washedwith pure water several times, and is neutralized with an alkali, andthen the product is again dehydrated to prepare a cellulose cake having20 to 50% by weight of solid content.

Preferably, in the cellulose powder according to the present invention,the cellulose cake is mixed with pure water to prepare a celluloseslurry having 10 to 25% by weight of solid content. It is preferablethat the cellulose slurry is stirred or the like to control the volumeaverage particle size of the particles in the cellulose dispersionliquid before drying to be 40 μm or more and less than 50 μm, and thenis spray dried. A volume average particle size of 40 μm or more ispreferred because the fluidity of the cellulose powder after drying isimproved. A volume average particle size of less than 50 μm is preferredbecause fluidity without demonstrating fibrous properties is improved.

The spray drying temperature can be 150 to 300° C., which is an inlettemperature typically used.

Stirring during the reaction or a subsequent step can reduce the lengthsof cellulose fibers. The volume average particle size of the particlescan be reduced by a larger stirring force, and can be increased by asmaller stirring force. The stirring force can be properly adjusted soas to attain a desired volume average particle size to control thevolume average particle size of the cellulose particle within the rangespecified in the present invention.

The stirring force can be adjusted by varying the size and shape of astirring tank, the size and shape of a stirring blade, the number ofrotations, the number of baffle plates, and the like.

After the reaction, the cellulose dispersion liquid is washed to adjustthe pH. This obtained cellulose dispersion liquid before dryingpreferably has an electric conductivity (IC) of 200 μS/cm or less. Whenan IC is 200 μS/cm or less, the dispersibility of the particles in waterand disintegration properties are improved. The IC is preferably 150μS/cm or less, more preferably 100 μS/cm or less. The cellulosedispersion liquid can be prepared with water or water containing a smallamount of an organic solvent in the range not to impair the effect ofthe present invention.

In the present invention, the natural cellulose substances indicatenatural-derived vegetable fibrous substances containing cellulose suchas wood materials, bamboo, cotton, and ramie, and preferably aresubstances having a crystal structure of cellulose I. From the viewpointof yield in preparation, the natural cellulose substances areparticularly preferably refined pulp products of these substances, whichdesirably contain 85% or more of α-cellulose.

The cellulose powder according to the present invention preferably has awater absorption capacity of 1.8 to 4.0 cm³/g. A water absorptioncapacity of 1.8 cm³/g or more is preferred because sugar coated tabletsare difficult to bond, and compactibility is also improved. A waterabsorption capacity of 4.0 cm³/g or less is preferred because anincrease in an amount of a liquid used for sugar coating does not impairdrying efficiency. A water absorption capacity of 3.5 cm³/g or less ispreferred because fibrous properties are barely demonstrated andfluidity and disintegration properties are high. The water absorptioncapacity is more preferably 1.8 to 3.0 cm³/g, particularly preferably1.8 to 2.8 cm³/g.

In the present invention, the molded article indicates molded articlesincluding the cellulose powder according to the present invention andproperly prepared by a known method selected from mixing, stirring,granulation, pressing, size regulation, drying, and the like. Examplesof molded articles used in pharmaceuticals include solid formulationssuch as tablets, powder medicines, subtle granules, granule agents,liquid extracts, pills, encapsulated formulations, lozenges, andpoultices. The molded article according to the present inventionincludes not only those used in pharmaceuticals but also those used infoods such as confections, health foods, texture improvers, and dietaryfiber strengthening agents, cake make-ups, bath agents, medicines foranimals, diagnostic agents, pesticides, fertilizers, ceramic catalysts,and the like.

In the present invention, the molded article may comprise the cellulosepowder according to the present invention in any content. The content ispreferably 1 to 99.9% by weight based on the weight of the moldedarticle. A content of 1% by weight or more can prevent abrasive wear orbreakage of the molded article to give sufficient physical properties.The content is preferably 3% by weight or more, preferably 5% by weightor more. The upper limit of the content of the cellulose powder is 99.9%by weight or less, more preferably 90% by weight or less from theviewpoint of efficacies of active ingredients.

Furthermore, in the present invention, the molded article may contain,in addition to the cellulose powder according to the present invention,optionally other additives such as active ingredients, disintegratingagents, binders, fluidizing agents, lubricants, flavoring substances,fragrances, colorants, sweeteners, and surfactants.

Examples of the disintegrating agent include celluloses such ascroscarmellose sodium, carmellose, carmellose calcium, carmellosesodium, and low substituted hydroxypropyl cellulose; starches such ascarboxy methyl starch sodium, hydroxypropyl starch, rice starch, wheatstarch, corn starch, potato starch, and partly pregelatinized starch;and crospovidone.

Examples of the binder include saccharides such as white sugar, glucose,lactose, and fructose; sugar alcohols such as mannitol, xylitol,maltitol, erythritol, and sorbitol; gelatin; water-solublepolysaccharides such as pullulan, carrageenan, locust bean gum, agar,glucomannan, xanthan gum, tamarind gum, pectin, alginic acid sodium, andgum arabic; celluloses such as microcrystalline cellulose, powdercellulose, hydroxypropyl cellulose, hydroxypropylmethyl cellulose, andmethyl cellulose; starches such as pregelatinized starch and starchglue; synthetic polymers such as polyvinylpyrrolidone, carboxyvinylpolymer, and polyvinyl alcohol; and inorganic substances such as calciumhydrogenphosphate, calcium carbonate, synthetic hydrotalcite, andmagnesium silicate aluminate.

Examples of the fluidizing agent include hydrous silicon dioxide andlight anhydrous silicic acid. Examples of the lubricant includemagnesium stearate, calcium stearate, stearic acid, sucrose fatty acidesters, and talc. Examples of the flavoring substances include glutamicacid, fumaric acid, succinic acid, citric acid, sodium citrate, tartaricacid, malic acid, ascorbic acid, sodium chloride, and 1-menthol.

Examples of the fragrances include oils such as orange, vanilla,strawberry, yogurt, menthol, fennel, cinnamon, picea, and peppermintoils; and green tea powder. Examples of the colorants include food dyessuch as food dye red No. 3, food dye yellow No. 5, and food dye blue No.1; sodium copper chlorophyllin, titanium oxide, and riboflavin. Examplesof the sweeteners include aspartame, saccharin, dipotassiumglycyrrhizinate, stevia, maltose, maltitol, mizuame, and powder ofHydrangea macrophylla var. thunbergii. Examples of the surfactantsinclude phosphorus lipid, glycerol fatty acid esters, polyethyleneglycol fatty acid esters, sorbitan fatty acid esters, andpolyoxyethylene hardened castor oil.

In the present invention, the active ingredient indicates activepharmaceutical ingredients, pesticide ingredients, fertilizeringredients, livestock food ingredients, food ingredients, cosmeticingredients, dyes, fragrances, metals, ceramics, catalysts, surfactants,and the like, and may be in any form of powder, crystal, oil, andsolution, for example. The active ingredient may be coated to controldissolution, reduce bitterness, and the like. The cellulose powderaccording to the present invention is particularly effective to theactive ingredients having bad odors.

Examples of active pharmaceutical ingredients include Kampo medicines,crude drugs, and natural and synthetic pharmaceuticals orallyadministrated and having bad odors, such as antipyretic analgesicantiphlogistics, hypnotics, antisleepiness drugs, antidizziness drugs,pediatric analgesics, stomachics, antacid, digestive drugs,cardiotonics, antiarrhythmic drugs, antihypertensives, vasodilators,diuretics, antiulcer drugs, intestinal regulators, antiosteoporosisdrugs, antitussive expectorants, antiasthmatic drugs, antibacterialdrugs, anti-pollakiuria drugs, analeptics, and vitamins.

Examples of Kampo medicines include:

ryokeikansoto, meiroinkakikuka, ryokeijutsukanto,ryokankyomishingeninto, ryutanshakanto, renjuin, ryokyojutsukanto,rikkunshito, rikkosan, ryokeimikanto, bushininjinto, mashiningan,makyoyokukanto, mokuboito, makyokansekito, maoto, maobushisaishinto,yohakusan, hontonto, hoyokangoto, yokuininto, hohaito,yokuibushihaisyosan, hochuekkito, yokukansan, yokukansankachimpihange,yokukansankasyakuyakuoren, hokikenchuto, heiisan, bunshoto, boiogito,boibukuryoto, huhiseimyakuto, bofutsushosan, bushikobeito,bukuryotakushato, bukuryoshigyakuto, bukuryokyoninkanzoto, hachigesan,hachimisenkiho, mibakujiogan, hangesyasinto, hangekobokuto,hangesankyuto, rokumigan, hatimijiogan, hangebyakujututenmato,bakumondoutou, byakujutusan, byakujutubusitou, hainoto, hainosan,hainosankyuto, byakkokaninjinto, byakkokakeisito, byakkoto,ninjinyoeito, bukuryukanto, busirityuto, ninjinto, bukuryoinkahange,bukuryoingohangekobokuto, bukuryoin, nyosinsan, teikiin, tibakujiogan,tikuyousekkoto, tyoyoto, toukakujokito, tennohosingan, tokisan, tudosan,tokisigyakukagosyuyusyokyoto, tokisigyakuto, tyoreitogosireito,tyoreito, tokisyakuyakusan, tokisyakuyakusankabusi,tokisyakuyakusankaninjin, tokisyakuyakusankaogityoto, tyotosan, tokito,tyokositeito, tokibaimokujinganryo, tyoijokito, dokkatsukiseito, tyuoko,dokkatuto, jizusoippo, nijututo, nitinto, jidabokuippo, daijokito,daisaikotokyodaio, daisaikoto, tyukentyuto, daikentyuto, daihangeto,daiobotanpito, daioubusito, daibouhuto, daiokanzoto, senkinkeimeisan,sankinnaitakusan, sensibyakujutusan, senkyutyatyosan, senkanmeimokuto,zokumeito, sessyoin, syozokumeito, seihaito, seinetuhoketuto,sokeikakketuto, seinetuhokito, sosikokito, seisinrensihin, sinbuto,sinpito, sinsentaituko, jinryobyakujututo, jingyobohuto,jingyokyokatuto, zensikunshito, jinsoin, shiniseihaito, seisituketanto,syoyosan (hatimisyoyosan), syohusan, seijokentsuto (kuhusyokutsuto),syobaito, seijobohuto, syomakakkonto, seisyoekkito, syohangekabukuryoto,syokyotoshinto, jasyosito, joganippou, syakosaito (sanmisyakosaito),juzentaihoto, jumihaidokuto, syakuyakukanzobushito, syakuyakukanzoto,juntyoto, syokentyuto, tokikentyuto, syakanzoto, syosaikoto,syosaikotokakikyosekko, seikiankaito, shiteito, syojokito,shichimotsukokato, tokiinshi, simotsuto, syoseiryuto,syoseiryutokasekko, syoseiryutokakyoninsekko, jijinmeimokuto, saisoin,saisyakurikkunshito, saikanto, sanmotsuougonto, sansouninto, jiinkokato,jiinshihoto, sanosyashinto, shiunko, satotsuko, shigyakuto,shigyakukaninjinto, shigyakusan, shikunshito, saireito, jiketsujunchoto,shikonboreito, saibokuto, shishishito, saikoseikanto, shishihakuhito,saikokeishito, jijintsujito, saikokeishikankyoto, kokikujiogan,kosharikkunshito, koshaheiisan, goshajinkigan, gokoto, shireito,goshuyuto, goreisan, gorinsan, takusyato, gomotsugedokusan, goshakusan,saikatsugekito, saikatsutokasenkyushini, goshitsusan, saikyohangeto,kososan, saikokaryukotsuboreito, kobokushokyohangeninjinkanzoto,saikosokanto, saikokikitsutokagomi, koshayoito, kishakunichinto,kigikenchyuto, keishakuchimoto, kyukikyogaito, kikyosekko,gedaishimotsuto, kenchutokeimakakuhanto, keimakakuhanto, keishikaogito,keishikakobokukyoninto, keishikakakkonto, keishito,keishikashakuyakushukyouninjinto, keishikashakuyakudaioto,keishikashakuyakuto, keikangan, keigairengyoto, keikyososooshinbuto,kumibinroto, kufugedokuto, keishikaryoujutsubuto, keishikajutsubuto,keishikaryukotsuboreito, kujinto, keishishakuyakuchimoto, gingyosan,kojito, keishibukurogankayokuinin, keishibukuryogan, gyokuheifusan,keihito, kyososan, keibohaidokusan, kyoseihatekigan, kanzobushito,kanzoshashinto, kanzokankyoto, kamiheiisan, kamishoyosankasenkyujio,kamishimotsuto, kashokuyouhito, kairoto (san), kaikyusyokusyoto,kamishoyosan, kakkonkajutsubuto, kamigedokuto, dokkatsukakkonto,kakkontokasenkyushin'i, kakkontokakkonkokato, karogaihakuto,karogaihakuhakusyuto, kakkon'oren'ogonto, kankyoninjinhangegan,kakkoshokisan, ogikeishigomotsuto, ogikenchuto, ogikenchuto, kanzoto,kanbakutaisoto, kagenryokakusan, kanroinotsujitokyodaio, otsujito,orento, kikyoto, orengedokuto, kamikihito, kihito, oren'akyoto,kyukichoketsuindaiichikagen, kyukichoketsuin, oshosan,keishinieppiittokajutsuto, keishinieppiitto, keishieppito,chikujountanto, kanbakutaisoto, unpito, eppikajutsuto, untanto, unseiin,ureitsukisan, unkeito, uyakujunkisan, inchingoreisan, anchusankabukuryo,inchinkoto, eppikajutsubuto, ifuto, en'nenhangeto and anchusan and soon. These ingredients may be processed powders of raw powders or extractpowders prepared by extracting raw powders, condensing the extracts, anddrying the extracts.

Examples of crude drugs include fennel, corydalis tuber, scutellariaroot, coptis rhizome, zedoary, Glycyrrhiza, Platycodon root, Curcumaaromatica, Schizonepeta spike, cinnamon bark, cyperus rhizome, magnoliabark, Gardenia fruit, cornus fruit, dioscorea rhizome, rehmannia root,lithospermum, peony root, amomum seed, ginger, processed ginger, Cnidiumrhizome, Atractylodes lancea rhizome, perilla herb, rhubarb, jujube,alisma tuber, clove, citrus unshiu peel, Japanese angelica root,eucommia bark, ginseng, mint, pinellia tuber, Atractylodes rhizome,Poria sclerotium, processed aconite root, Saposhnikovia root andrhizome, moutan bark, oyster shell, Ephedra herb, Alpinia officinarumHance, Forsythia fruit, and deer antler velvet. Examples of theingredients contained in Bofutsushosan include Ephedra herb (Ephedrasinica Stapf, Ephedra intermedia Schrenk et C. A. Meyer, Ephedraequisetina Bunge), Glycyrrhiza (Glycyrrhiza uralensis Fischer,Glycyrrhiza glabra Linne), ginger (Zingiber officinale Roscoe),Schizonepeta spike (Schizonepeta tenuifolia Briquet), Forsythia fruit(Forsythia suspense Vahl, Forsythia viridissima Lindley), Japaneseangelica root (Angelica acutiloba Kitagawa, Angelica acutiloba Kitagawavar. sugiyamae Hikino), peony root (Paeonia lactiflora Pallas), cnidiumrhizome (Cnidium officinale Makino), Gardenia fruit (Gardeniajasminoides Ellis), mint (Mentha arvensis Linne var. piperascensMalinvaud), Saposhnikovia root and rhizome (Saposhnikovia divaricataSchischkin), rhubarb (Rheum palmatum Linne, Rheum tanguticum Maximowicz,Rheum officinable Baillon, Rheum coreanum Nakai, or interspecifichybrids thereof), Atractylodes rhizome (Atractylodes japonica Koidzumiex Kitamura, Atractylodes ovata De Candolle), Platycodon root(Platycodon grandiflorum A. De Candolle), and scutellaria root(Scutellariae baicalensis Georgi). These ingredients may be processedpowders of raw powders or extract powders prepared by extracting rawpowders, condensing the extracts, and drying the extract.

The content of the active ingredient in the molded article according tothe present invention is preferably 0.01 to 99% by weight based on theweight of the molded article. At a content of the active ingredient of0.01% by weight or more, sufficient efficacy can be expected. At acontent of 99% by weight or less, abrasive wear or breakage of themolded article can be prevented by a sufficient amount of an excipientto give satisfactory physical properties to the molded articles.

In the present invention, the tablet indicates a molded articleincluding the cellulose powder according to the present invention andoptional other additives, which can be prepared by one of a directcompression tableting method, a granule compression method, and wetgranulation compression (extragranular addition of cellulose powder).Among these, tablets prepared by the direct compression tableting methodare particularly preferred.

Among the molded articles according to the present invention, preferablythe tablets, when the tablet contains one or more active ingredients andone or more additives selected from saccharides, sugar alcohols,starches, and disintegrating agents, compounding of the cellulose powderaccording to the present invention attains a molded article, preferablya tablet having a hardness of 50 to 200 N, a tensile strength of 0.1 to12 MPa, a friability of 0 to 0.5%, a swelling rate of the diameter ofthe molded article, preferably the tablet in acetone of 0 to 3.3%. Theamount of the cellulose powder compounded with the molded article,preferably the tablet is preferably 5 to 90% by weight. An amount ofcompounding in the range of 5 to 90% by weight is preferred becausephysical properties described above are well-balanced.

The compounding of the cellulose powder according to the presentapplication with a molded article, preferably a tablet can attain atablet having a hardness, a tensile strength, and a friability in theranges above, a swelling rate of the diameter of the molded article,preferably the tablet in acetone of 0 to 3.3%. The swelling rate of thediameter of the molded article, preferably the tablet in acetone ispreferably 0 to 3%, more preferably 0 to 2%. A swelling rate of thediameter of the molded article, preferably the tablet in acetone in therange of 0 to 3.3% is preferred because the hardness, the tensilestrength, and the friability are well-balanced.

The swelling rate of the diameter of the molded article, preferably thetablet in acetone is defined by a rate of change in the diameter (mm) ofthe molded article (preferably tablet) before and after the moldedarticle (the tablet) is dipped in acetone (25° C.) for 60 seconds, andis calculated by the following expression:swelling rate (%) of diameter of molded article (tablet)=[(diameter ofmolded article (tablet) after dipping in acetone)−(diameter of moldedarticle (tablet) before dipping in acetone)/(diameter of molded article(tablet) before dipping in acetone)]×100

High compactibility of the cellulose powder according to the presentinvention results in a low swelling rate of the diameter of the moldedarticle, preferably the tablet in acetone. A number of drugs have poorcompactibility. If such a drug is contained in a molded article,preferably a tablet in a higher content, the physical properties of thedrug are reflected. The resulting molded article (tablet) has lowhardness and is readily worn. At this time, with a cellulose powderhaving insufficient compactibility, a molded article, preferably atablet having a hardness of 50 N or more and a friability of 0.5% orless may not be attained. In contrast, use of the cellulose powderaccording to the present invention can give a hardness and friabilitysuitable for practical use to the molded article, preferably thetablets. A preferred range of a drug contained in the molded article,preferably the tablet is 30 to 90% by mass, preferably 50 to 80% bymass. The content in the range of 30 to 90% by mass are preferred fromthe viewpoint of hardness and friability.

If the swelling rate of the diameter of the molded article, preferablythe tablet in acetone is 0 to 3.3%, the resulting molded article,preferably the tablet can disintegrate and dissolve quickly. The amountof total organic carbon derived from the residual impurities in themolded article residues or in the cellulose powder obtained throughwashing of the molded article, preferably the tablet with acetone,ethanol, pure water, and ethanol sequentially and extraction ispreferably more than 0.07 and 0.3% or less. The amount in the range ofmore than 0.07 and 0.3% or less is preferred from the viewpoint ofcompactibility. An amount of total organic carbon derived from residualimpurities of 0.09 to 0.15% is preferred from the viewpoints of badodors suppression, whiteness, and gloss.

The amount of total organic carbon derived from the residual impuritiesin the molded article, preferably the tablet residues is defined by thedifference (%) between the amount of total organic carbon (TOC) in themolded article residues extracted from the molded article residues withpure water (80 mL) and the amount of TOC in the molded article residuesextracted from the molded article residues with an aqueous solution of1% sodium hydroxide (80 mL). When the molded article residues arecellulose powder, the molded article residues are sufficiently washedwith pure water. For this reason, the amount of total organic carbon (%)during extraction with pure water in the molded article residues isclose to zero, and the amount of total organic carbon derived from theresidual impurities in the molded article residues is substantiallyequal to the amount of total organic carbon (%) during extraction with1% NaOH. When the amount of total organic carbon (%) during extractionwith pure water is detected, removal of impurities by washing with purewater may be insufficient or removal of acetone and ethanol residuals bydrying may be insufficient. For this reason, the amount of pure waterused in extraction is increased 1.3 to 2 times, or the dryingtemperature is adjusted to 100 to 120° C. and the drying time isadjusted to 3 to 5 hr. The amount of total organic carbon derived fromthe residual impurities in the molded article residues obtained throughwashing of the molded article with acetone, ethanol, pure water, andethanol sequentially and extraction can be checked by the followingprocedure.

(i) 120 g of a molded article is placed in a 500 ml beaker, and 300 g ofacetone is added. The mixture is stirred with a stirrer until moldedarticle fragments disappear. The solution is vacuum filtered (with aBuchner funnel, and a filter paper for quantitative analysis, 5 C,diameter: 110 mm). When molded article fragments are found, the solutionis subjected to ultrasonic treatment for 10 minutes, and is stirred for30 minutes. This operation is repeated until the molded articlefragments disappear.

(ii) 100 mL of ethanol is added to the residues on the filter paper, ismixed with the residues with a spatula sufficiently, and is vacuumfiltered (this operation is repeated 3 times). The ingredients barelysoluble in water are removed by the operations (i) and (ii).

(iii) The residues treated in (ii) are added to 1000 mL of pure water,is stirred with a stirrer for 10 minutes, and is vacuum filtered.

(iv) The residues treated in (iii) are added to 600 ml of pure water, isstirred with a stirrer for 10 minutes, and is vacuum filtered.

(v) The residues treated in (iv) are added to 1000 mL of pure water, andthe mixture is heated at 80 to 100° C. for 30 minutes while the mixtureis stirred with a stirrer. After cooling to 20 to 30° C., 5 μg/L ofα-amylase is added, is stirred at 37° C. for 30 minutes, and is vacuumfiltered.

(vi) 150 mL of ethanol is added to the residues treated in (v). Theresidues are mixed with a spatula sufficiently, and is vacuum filtered(this operation is repeated 3 times). The water-soluble ingredients andstarches are removed by the operations (iii) to (vi). The water-solubleingredients include saccharides and sugar alcohols, and can bedetermined by a known method.

(vii) The residues on the filter paper are scraped off therefrom, andare placed in a petri dish. The residues are dried at room temperature(20 to 30° C.) until a smell of ethanol disappears, and are dried at100° C. for 3 hours to prepare a sample for measurement.

(viii) About 2 g of the dried residues are placed in a cell formeasurement, and are measured by near-infrared spectroscopy. Thus, anabsorption spectrum is obtained (name of the apparatus: InfraAlyzer 500,manufacturer: BRAN+LUBBE). When the peaks indicating second derivativevalues are detected at 1692 nm in an NIR absorption spectrum, thecellulose powder content (C (%)) in the molded article residues iscalculated by the following expression:C (%)=intensity of NIR second derivative spectrum×316583+95.588

When the peaks indicating the second derivative values in the NIRabsorption spectrum are found at 1692 nm, crospovidone residues arecontained in addition to the cellulose powder. The content of thecellulose powder in the dried residues is determined by the aboveexpression. Instead of the molded article in (i), three compositionpowders of cellulose powder/crospovidone=100/0, 50/50, and 0/100 areprepared. Through the operations (i) to (vii), dried residues are eachprepared. The intensities of the NIR second derivative spectrums aremeasured with the InfraAlyzer 500 (manufacturer: BRAN+LUBBE). From thethree calibration curves, the coefficients in the above expression canbe determined.

When no peaks of second derivative values in the NIR absorption spectrumare detected at 1692 nm, and the amount of total organic carbon (TOC)extracted with pure water (80 mL) from the dried residues in the driedresidues is 0.0%, the dried residues are composed of only the cellulosepowder. At an amount of TOC of more than 0.0%, disintegrating agentsother than starch and crospovidone may be contained. To remove these,dried residues are dispersed in 50 mL of pure water, and are passedthrough a sieve having an opening of 10 μm to remove particles otherthan the cellulose powder. The filtrate is evaporated, and the resultingproduct is dried and solidified to prepare dried residues in (ix). Whenthe amount of total organic carbon (%) in the residues during extractionwith pure water exceeds 0.0% even after this operation, the driedresidues are dispersed in 50 mL of pure water (may be optionallysubjected to ultrasonic and homogenizing treatments), and arecentrifuged at 2000 G. The supernatant is evaporated, and the resultingproduct is dried and solidified to prepare dried residues in (ix).

(ix)<Case where Peaks of Second Derivative Values in NIR AbsorptionSpectrum are Detected at 1692 nm in (viii)>

The dried residues (A (g), 4 to 4.5 g as a guideline) are weighed, andare added to 80 ml of 1% NaOH. The mixture is stirred with a stirrer for5 minutes, and is vacuum filtered. The filtrate is extracted to measurethe volume (X (mL)). The filtrate is acidified with hydrochloric acid(pH: 2 to 3). The amount of total organic carbon (TOC_(1% NaOH) (mg/L))is measured with a total organic carbon analyzer (manufactured bySHIMADZU Corporation, TOC-VCSH, by a TC-IC method). Because the residuesare sufficiently washed with pure water, the amount of total organiccarbon (%) during extraction with pure water is considered as zero.Accordingly, the amount of organic carbon derived from the residualimpurities in the cellulose powder contained in the residue is equal tothe amount of total organic carbon (%) during extraction with 1% NaOH.Calculation is performed as follows:amount of cellulose powder residue (B (g)) in residue extracted frommolded article=A×C/100amount of total organic carbon (Y (mg)) in cellulose powderresidue=(TOC_(1% NaOH)/1000)×X−0.4/100×(A−B)×1000

The coefficient 0.4 is the amount of total organic carbon (%) when 2.5 gof a crospovidone powder is used as the molded article in (i) to preparedried residues through the treatments to (vii), and the dried residuesare extracted with 80 ml of 1% NaOH.amount of total organic carbon (%) derived from residual impurities inmolded article residues obtained through washing of the molded articlewith acetone, ethanol, pure water, and ethanol sequentially andextraction=Y/(1000×B)×100=Y/(10×B)<Case where Peaks of Second Derivative Values in NIR Absorption Spectrumare not Detected at 1692 nm in viii)>

The dried residues (A_(H2O) (g): during extraction with pure water,A_(1% NaOH) (g): during extraction with a 1% NaOH aqueous solution) areweighed, and 80 mL of pure water or 1% NaOH aqueous solution is added.The mixture is stirred in a beaker for 5 minutes (with a stirrer), andis vacuum filtered (with a filter paper for quantitative analysis, 5 C,diameter: 110 mm) to remove the dried residues and obtain a filtrate.After the volume of the total amount of the filtrate (V_(H2O): totalamount (mL) in use of pure water, V_(1% NaOH): total amount (mL) in useof 1% NaOH) is measured, the filtrate is acidified with hydrochloricacid (pH: 2 to 3), and the amount of total organic carbon (TOC (mg/L))was measured with a total organic carbon analyzer (manufactured bySHIMADZU Corporation, TOC-VCSH, by a TC-IC method). The TOC in use ofpure water is TOC_(H2O), and the TOC in use of 1% NaOH is TOC_(1% NaOH).The amount of organic carbon derived from the residual impurities in themolded article residues is calculated by the following expressions:amount of total organic carbon (%) derived from residual impurities inmolded article residues=amount of total organic carbon (%) duringextraction with 1% NaOH−amount of total organic carbon (%) duringextraction with pure wateramount of total organic carbon (%) during extraction with 1%NaOH:=[(TOC_(1% NaOH) (mg/L)/1000)×V _(1% NaOH) (mL)]/A _(1% NaOH)×1000(mg)×100amount of total organic carbon (%) during extraction with purewater:=[(TOC_(H2O) (mg/L)/1000)×V _(H2O) (mL)]/A _(H2O)×1000 (mg)×100

The cellulose powder according to the present invention can be used inwet granulation as a sugar-coating reinforcing agent in sugar-coatedtablets, an extruding property improver in extrusion granulation, andgranulation aids in crush granulation, fluidized bed granulation, highspeed high shear granulation, tumbling granulation, and the like toprepare granule agents and granules for pressing. The granules forpressing can be prepared by dry granulation. Furthermore, tablets can beprepared by a method (wet granulation compression (extragranularaddition of cellulose powder)) in which the cellulose powder accordingto the present invention is added to the granules for pressing preparedby such a known method, and the mixture is compressed. The cellulosepowder according to the present invention can delay the granulation ratewhen active pharmaceutical ingredients having high moisture absorbingproperties and high water solubility are granulated, so that generationof coarse particles are reduced to increase granulation yield. Thecellulose powder according to the present invention, which has a lowparticle density, provides bulky granulated products. For this reason,the cellulose powder contributes to preparation of granules for pressinghaving high compression compactibility. The cellulose powder accordingto the present invention can be compounded with powder medicines to, forexample, prevent blocking and improve fluidity, or can be compoundedwith encapsulated formulations to, for example, improve fillingproperties.

EXAMPLES

The present invention will now be described in more detail by way ofExamples, but the scope of the present invention will not be limited tothese. Physical properties in Examples and Comparative Examples weremeasured by the following methods.

1) Average Degree of Polymerization (−)

The average degree of polymerization is a value determined by a copperethylene diamine solution viscosity method described in amicrocrystalline cellulose check test (3) in the 15th edition of thePharmacopeia of Japan.

2) Loss on Drying (%)

1 g of a powder was dried at 105° C. for 3 hours, and the amount ofweight reduction was expressed by weight percentage.

3) Volume Average Particle Size (μm) of Cellulose Particle in CelluloseDispersion Liquid

The particle size of particles in the cellulose dispersion liquid afterhydrolysis or before drying was determined by the following procedure. Acellulose dispersion liquid was dropped onto a microscope stand. A glassslide was placed over the droplets. The droplets were dried, and anoptical microscopic image was taken with a microscope. The opticalmicroscopic image was subjected to image analysis processing(manufactured by Inter Quest Co., Ltd., apparatus: Hyper 700, software:Imagehyper). Among rectangles circumscribing a particle, the long sideof the rectangle having the smallest area was determined, and thecumulative number 50% particle size was defined as the volume averageparticle size. At least 100 or more particles were subjected to imageanalysis processing.

4) Weight Average Particle Size (μm) of Cellulose Powder

The weight average particle size of a powder sample was determined bysieving 10 g of the sample with a low tapping sieve shaker (sieve shakertype A manufactured by Heiko Seisakusho, Ltd.) and a JIS standard sieve(Z8801-1987) for 10 minutes to determine the particle size distribution.The particle size distribution was expressed as a cumulative weight 50%particle size.

5) Apparent Specific Volume (cm³/g)

A powder sample was roughly placed in a 100 cm³ glass measuring cylinderwith a constant volume feeder or the like over 2 to 3 minutes. The topsurface of the powder layer was leveled with a soft brush like an inkbrush. The volume thereof was read, and was divided by the weight of thepowder sample to determine the apparent specific volume. The weight ofthe powder was properly determined to have a volume of about 70 to 100cm³.

6) Apparent Tapping Density (g/cm³)

With a commercially available powder physical property analyzer(manufactured by Hosokawa Micron Corporation, powder tester type PT-R),a powder was placed in a 100 cm³ cup, and was tapped 180 times. Thevolume of the cup was divided by the weight of the powder layerremaining in the cup to determine the apparent tapping density.

7) Intraparticle Pore Volume (cm³/g)

Pore distribution was determined with AutoPore, type 9520 (trade name)manufactured by SHIMADZU Corporation by mercury porosimetry. The samplepowders used in the measurement were dried at room temperature for 15hours under reduced pressure. From the pore distribution determined inthe measurement at an initial pressure of 20 kPa, the total volume ofpores having a diameter of 0.1 to 15 μm was defined as the intraparticlepore volume.

8) Amount of Organic Carbon (%) Derived from Residual Impurities

80 mL of pure water or a 1% NaOH aqueous solution was added to acellulose powder (W (mg), 5000 mg as a guideline), and was stirred for 5minutes in a beaker (with a stirrer). Then, the cellulose powder wasremoved through vacuum filtration (with a filter paper for quantitativeanalysis, 5 C, diameter: 110 mm) to obtain a filtrate. The total volumeof the filtrate was measured (where the total volume in use of water wasV_(H2O), and the total volume in use of 1% NaOH was V_(1% NaOH) (mL)),and the filtrate was acidified with hydrochloric acid (pH: 2 to 3).Then, the amount of total organic carbon (TOC (mg/L)) was measured witha total organic carbon analyzer (manufactured by SHIMADZU Corporation,TOC-VCSH, by a TC-IC method). The TOC in use of pure water wasTOC_(H2O), and the TOC in use of 1% NaOH was TOC_(1% NaOH). The amountof organic carbon derived from the residual impurities was calculated bythe following expressions:amount of organic carbon (%) derived from residual impurities=amount oftotal organic carbon (%) during extraction with 1% NaOH−amount of totalorganic carbon (%) during extraction with pure wateramount of total organic carbon (%) during extraction with 1%NaOH:=[(TOC_(1% NaOH) (mg/L)/1000)×V _(1% NaOH) (mL)]/W (mg)×100amount of total organic carbon (%) during extraction with purewater:=[(TOC_(H2O) (mg/L)/1000)×V _(H2O) (mL)]/W (mg)×1009) Water Absorption Capacity (cm³/g)

Pure water was dropped to 2 g of a cellulose powder (in terms of driedpowder), and when necessary the cellulose powder was kneaded with aspatula or the like so as to be mixed with the dropped water. A pointwhen water bled out on the surface of the mixture was defined as an endpoint, and the amount of pure water dropped (V) was determined. Thewater absorption capacity was calculated by the following expression.The average value of three values obtained in the measurement was used.Water absorption capacity (cm³/g)=V/210) Angle of Repose (°)

Using a Sugihara type repose angle measuring apparatus (slit size:depth: 10 mm, width: 50 mm, height: 140 mm, a protractor was disposed ata position of a width of 50 mm), the dynamic self-fluidity was measuredwhen the cellulose powder was dropped into the slit with a constantvolume feeder at a rate of 3 g/min. The angle formed by the bottomsurface of the apparatus and the formed layer of the cellulose powder isan angle of repose.

11) Hardness (N)

Cylindrical molded articles or tablets were broken with a Schleunigerdurometer (manufactured by Freund Corporation, type 6D) by applying aload in the diameter direction of the cylindrical molded article or thetablet, and the load at this time was measured. The hardness wasexpressed as the number average of five samples. A cylindrical moldedarticle composed of 100% cellulose powder was prepared as follows. 0.5 gof a sample was placed in a die (manufactured by Kikusui SeisakushoLtd., material SUK2, 3 was used), and was compressed at 10 MPa with aflat-surface punch (manufactured by Kikusui Seisakusho Ltd., materialSUK2, 3 was used) having a diameter of 1.13 cm (bottom area: 1 cm²). Thestress was kept for 10 seconds to prepare a cylindrical molded article(a compressor manufactured by AIKOH ENGINEERING CO., LTD., PCM-1A wasused, the compression rate was about 10 cm/min). The hardness suitablefor practical use is 50 N or more in the tablet having a diameter of 8mm and is 70 N or more in the tablet having a diameter of 9 mm or more.

12) Tensile Strength (MPa)

The hardness of a tablet: H (N), the diameter of the tablet (the largestdiameter was used in caplets or the like): D (mm), and the thickness ofthe tablet: T (mm) were determined, and the tensile strength wascalculated by the following expression:tensile strength (MPa)=2×H/(3.14×D×T)13) Friability of Tablet (%)

The weights (Wa) of 20 tablets were measured. These tablets were placedin a tablet friability tester (PTFR-A, manufactured by Pharma TestApparatebau AG), and were rotated at 25 rpm for 4 minutes. Then, finepowders adhering to the tablets were removed, and the weights (Wb) wereagain measured. The friability was calculated by the expression (7):friability=100×(Wa−Wb)/Wa

Tablets suitable for practical use should have a friability of 0.5% orless.

14) Sensory Evaluation on Tablet

Bofutsushosan extract alone or 20 tablets containing Bofutsushosan wereplaced in a 100 mL glass air-tight bottle. After 30 minutes had passed,the bottle was opened to evaluate the odor. Ten evaluators who weresensitive to odors evaluated the odor on a five-level rating systemwhere the odor from the dry extract of Bofutsushosan alone was rated as3. A larger value indicated that the bad odor was reduced and an aromawas likely to be increased. If the odor from the dry extract ofBofutsushosan alone was only masked to make the odor weaker, the samplewas rated as “0.”

15) Whiteness of Tablet (%)

The values L, a, and b were determined with a spectrocolorimeter(SE-2000, manufactured by Nippon Denshoku Industries Co., Ltd.) tocalculate the whiteness by the following expression:whiteness=100−[(100−L)²+(a ² +b ²)]^(0.5)

L: brightness, a: saturation (green to red), b: saturation (blue toyellow)

16) Gloss of Tablet

The gloss was visually evaluated on the following 4-level rankingsystem:

⊚: gloss over the tablet

◯: gloss on most of the tablet

Δ: gloss on part of the tablet

x: no gloss

Example 1

2 kg of a commercially available SP pulp (degree of polymerization:1030, level-off degree of polymerization: 220) was shredded, and wasadded to 30 L of an aqueous solution of 0.05% hydrochloric acid. Whilethe mixture was stirred (at a stirring rate of 234 rpm) with a low speedstirrer (manufactured by Ikebukuro Horo Kogyo Co., Ltd., 30 LGL reactor,blade diameter: about 30 cm), the pulp was hydrolyzed at 145° C. for 70minutes. The resulting acid-insoluble residues were filtered with asuction funnel. The filtered residues were washed with 70 L of purewater 4 times, and were neutralized with aqueous ammonia. The residueswere placed in a 90 L plastic bucket, and pure water was added. Whilethe mixture was stirred (at a stirring rate of 500 rpm) with a three-onemotor (manufactured by HEIDON, type BLh1200, 8 M/M, blade diameter:about 10 cm), a cellulose dispersion liquid having a concentration of16% was prepared (pH: 7.8, IC: 55 μS/cm).

The cellulose dispersion liquid was spray dried (liquid feed rate: 6L/hr, inlet temperature: 180 to 220° C., outlet temperature: 50 to 70°C.) to prepare Cellulose powder A (loss on drying: 4.0%). The physicalproperties of Cellulose powder A and the physical properties of acylindrical molded article prepared by compressing 100% Cellulose powderA are shown in Table 1.

Example 2

2 kg of a commercially available SP pulp (degree of polymerization:1030, level-off degree of polymerization: 200) was shredded, and wasadded to 30 L of an aqueous solution of 0.08% hydrochloric acid. Whilethe mixture was stirred (at a stirring rate of 234 rpm) with a low speedstirrer (manufactured by Ikebukuro Horo Kogyo Co., Ltd., 30 LGL reactor,blade diameter: about 30 cm), the pulp was hydrolyzed at 140° C. for 110minutes. The resulting acid-insoluble residues were filtered with asuction funnel. The filtered residues were washed with 70 L of purewater 4 times, and were neutralized with aqueous ammonia. The residueswere placed in a 90 L plastic bucket, and pure water was added. Whilethe mixture was stirred (at a stirring rate of 500 rpm) with a three-onemotor (manufactured by HEIDON, type BLh1200, 8 M/M, blade diameter:about 10 cm), a cellulose dispersion liquid having a concentration of18% was prepared (pH: 7.5, IC: 60 μS/cm).

The cellulose dispersion liquid was spray dried (liquid feed rate: 6L/hr, inlet temperature: 180 to 220° C., outlet temperature: 50 to 70°C.) to prepare Cellulose powder B (loss on drying: 3.5%). The physicalproperties of Cellulose powder B and the physical properties of acylindrical molded article prepared by compressing 100% Cellulose powderB are shown in Table 1.

Example 3

2 kg of a commercially available KP pulp (degree of polymerization:1030, level-off degree of polymerization: 190) was shredded, and wasadded to 30 L of an aqueous solution of 0.10% hydrochloric acid. Whilethe mixture was stirred (at a stirring rate of 234 rpm) with a low speedstirrer (manufactured by Ikebukuro Horo Kogyo Co., Ltd., 30 LGL reactor,blade diameter: about 30 cm), the pulp was hydrolyzed at 135° C. for 100minutes. The resulting acid-insoluble residues were filtered with asuction funnel. The filtered residues were washed with 70 L of purewater 4 times, and were neutralized with aqueous ammonia. The residueswere placed in a 90 L plastic bucket, and pure water was added. Whilethe mixture was stirred (at a stirring rate of 500 rpm) with a three-onemotor (manufactured by HEIDON, type BLh1200, 8 M/M, blade diameter:about 10 cm), a cellulose dispersion liquid having a concentration of19% was prepared (pH: 7.5, IC: 50 μS/cm).

The cellulose dispersion liquid was spray dried (liquid feed rate: 6L/hr, inlet temperature: 180 to 220° C., outlet temperature: 50 to 70°C.) to prepare Cellulose powder C (loss on drying: 3.3%). The physicalproperties of Cellulose powder C and the physical properties of acylindrical molded article prepared by compressing 100% Cellulose powderC are shown in Table 1.

Example 4

2 kg of a commercially available KP pulp (degree of polymerization:1030, level-off degree of polymerization: 130) was shredded, and wasadded to 30 L of an aqueous solution of 0.15% hydrochloric acid. Whilethe mixture was stirred (at a stirring rate of 80 rpm) with a low speedstirrer (manufactured by Ikebukuro Horo Kogyo Co., Ltd., 30 LGL reactor,blade diameter: about 30 cm), the pulp was hydrolyzed at 110° C. for 105minutes. The resulting acid-insoluble residues were filtered with asuction funnel. The filtered residues were washed with 70 L of purewater 4 times, and were neutralized with aqueous ammonia. The residueswere placed in a 90 L plastic bucket, and pure water was added. Whilethe mixture was stirred (at a stirring rate of 500 rpm) with a three-onemotor (manufactured by HEIDON, type BLh1200, 8 M/M, blade diameter:about 10 cm), a cellulose dispersion liquid having a concentration of19% was prepared (pH: 7.5, IC: 65 μS/cm).

The cellulose dispersion liquid was spray dried (liquid feed rate: 6L/hr, inlet temperature: 180 to 220° C., outlet temperature: 50 to 70°C.) to prepare Cellulose powder D (loss on drying: 3.2%). The physicalproperties of Cellulose powder D and the physical properties of acylindrical molded article prepared by compressing 100% Cellulose powderD are shown in Table 1.

The cellulose powders according to the present application (Examples 1to 4) have about 20 to 30% higher compactibility than that of theconventional cellulose powders (Comparative Examples 1 and 2) even whenthe apparent specific volume is the same, as shown in FIG. 1.

Example 5

Cellulose powder E was prepared by the same operation as in Example 3except that the concentration of hydrochloric acid was 0.16%.

The physical properties of Cellulose powder E and the physicalproperties of a cylindrical molded article prepared by compressing 100%Cellulose powder E are shown in Table 1.

Example 6

Cellulose powder F was prepared by the same operation as in Example 3except that hydrolysis time was 120 minutes.

The physical properties of Cellulose powder F and the physicalproperties of a cylindrical molded article prepared by compressing 100%Cellulose powder F are shown in Table 1.

Example 7

Cellulose powder G was prepared by the same operation as in Example 3except that the hydrolysis time was 60 minutes.

The physical properties of Cellulose powder G and the physicalproperties of a cylindrical molded article prepared by compressing 100%Cellulose powder G are shown in Table 1.

Example 8

Cellulose powder H was prepared by the same operation as in Example 3except that the hydrolysis temperature was 90° C.

The physical properties of Cellulose powder H and the physicalproperties of a cylindrical molded article prepared by compressing 100%Cellulose powder H are shown in Table 1.

Example 9

Cellulose powder I was prepared by the same operation as in Example 1except that the hydrolysis time was 45 minutes.

The physical properties of Cellulose powder I and the physicalproperties of a cylindrical molded article prepared by compressing 100%Cellulose powder I are shown in Table 1.

Example 10

Cellulose powder J was prepared by the same operation as in Example 2except that the concentration of hydrochloric acid was 0.28%, thehydrolysis temperature was 110° C., and the hydrolysis time was 60minutes.

The physical properties of Cellulose powder J and the physicalproperties of a cylindrical molded article prepared by compressing 100%Cellulose powder J are shown in Table 1.

Example 11

Cellulose powder K was prepared by the same operation as in Example 3except that the concentration of hydrochloric acid was 0.08%, thehydrolysis temperature was 135° C., and the hydrolysis time was 80minutes.

The physical properties of Cellulose powder K and the physicalproperties of a cylindrical molded article prepared by compressing 100%Cellulose powder K are shown in Table 1.

Comparative Example 1

2 kg of a commercially available SP pulp (degree of polymerization:1030, level-off degree of polymerization: 220) was shredded, and washydrolyzed with 30 L of an aqueous solution of 0.14 N (0.49%)hydrochloric acid at 121° C. for 1 hour. The resulting acid-insolubleresidues were filtered with a suction funnel. The filtered residues werewashed with 70 L of pure water 4 times, and were neutralized withaqueous ammonia. The residues were placed in a 90 L plastic bucket.While the mixture was stirred with a three-one motor, a cellulosedispersion liquid having a concentration of 17% was prepared (pH: 6.4,IC: 64 μS/cm).

The cellulose dispersion liquid was spray dried (liquid feed rate: 6L/hr, inlet temperature: 180 to 220° C., outlet temperature: 70° C.),and coarse particles were removed with a 325 mesh sieve to prepareCellulose powder L (loss on drying: 4.1%, corresponding to Example 1 inJP 40-26274 B). The physical properties of Cellulose powder L and thephysical properties of a cylindrical molded article prepared bycompressing 100% Cellulose powder L are shown in Table 1.

Comparative Example 2

A commercially available KP pulp (degree of polymerization: 840,level-off degree of polymerization: 145) was hydrolyzed in an aqueoussolution of 0.7% hydrochloric acid at 125° C. for 150 minutes. Thehydrolyzed residues were neutralized, were washed, and were filtered toprepare a wet cake. The wet cake was sufficiently ground with a kneader.Ethanol was added in a volume ratio of ethanol to the wet cake of 1:1.The solution was compression filtered, and was dried with air. The driedpowder was milled with a hammer mill, and coarse particles were removedwith a 40 mesh sieve to prepare Cellulose powder M (dry weight: 3.0%,corresponding to Example 1 in JP 56-2047 A). The physical properties ofCellulose powder M and the physical properties of a cylindrical moldedarticle prepared by compressing 100% Cellulose powder M are shown inTable 1.

Comparative Example 3

Cellulose powder N was prepared by the same operation as in Example 3except that the hydrolysis temperature was 160° C. The physicalproperties of Cellulose powder N and the physical properties of acylindrical molded article prepared by compressing 100% Cellulose powderN are shown in Table 1.

Comparative Example 4

Cellulose powder O was prepared by the same operation as in Example 3except that the hydrolysis temperature was 90° C., and the hydrolysistime was 50 minutes. The physical properties of Cellulose powder O andthe physical properties of a cylindrical molded article prepared bycompressing 100% Cellulose powder O are shown in Table 1.

Comparative Example 5

Cellulose powder P was prepared by the same operation as in Example 1except that the hydrolysis temperature was 25° C., and the hydrolysistime was 30 minutes. The physical properties of Cellulose powder P andthe physical properties of a cylindrical molded article prepared bycompressing 100% Cellulose powder P are shown in Table 1.

Comparative Example 6

Cellulose powder Q was prepared by the same operation as in Example 2except that the concentration of hydrochloric acid was 0.50%, thehydrolysis temperature was 90° C., and the hydrolysis time was 35minutes. The physical properties of Cellulose powder Q and the physicalproperties of a cylindrical molded article prepared by compressing 100%Cellulose powder Q are shown in Table 1.

TABLE 1 Physical properties of cellulose Reactions dispersion conditionsliquid Physical Concen- Volume Volume properties of tration averageaverage cellulose powder of Hydro- particle particle Average Weighthydro- lysis Hydro- size size degree of average chloric temper- lysis(μm) (μm) polymeri- particle Cellulose acid ature time after beforezation size powder (%) (° C.) (min) reaction drying (−) (μm) Example 1 A0.05 145 70 146 49 280 40 2 B 0.08 140 110 120 47 200 80 3 C 0.10 135100 115 45 100 50 4 D 0.15 110 105 70 40 130 240 5 E 0.16 135 100 65 38120 56 6 F 0.10 135 120 80 43 180 44 7 G 0.10 135 60 151 55 180 59 8 H0.10 90 100 180 65 330 70 9 I 0.05 145 45 156 54 330 40 10 J 0.28 110 60120 47 185 45 11 K 0.08 135 80 123 44 200 80 Comparative 1 L 0.49 121 6065 30 220 49 Example 2 M 0.70 125 150 50 25 145 40 3 N 0.10 160 100 6328 170 45 4 O 0.10 90 50 210 75 400 35 5 P 0.05 25 30 294 110 580 210 6Q 0.50 90 35 170 75 360 90 Physical properties of cellulose powderCylindrical Amount molded of article organic composed carbon of (%)Intra- 100% Apparent Angle derived particle Water cellulose specificTapping of from pore absorption powder volume density repose residualvolume capacity Hardness (cm³/g) (g/cm³) (°) impurities (cm³/g) (cm³/g)(N) Example 1 3.9 0.32 43 0.145 0.25 3.0 75 2 3.3 0.45 38 0.131 0.21 2.570 3 3.1 0.51 42 0.116 0.20 2.3 65 4 2.6 0.59 36 0.090 0.12 1.8 55 5 2.50.58 38 0.085 0.21 1.9 48 6 2.5 0.61 37 0.080 0.19 1.8 47 7 4.2 0.29 480.152 0.20 3.5 88 8 5.0 0.22 54 0.164 0.22 4.0 90 9 10.0 0.21 56 0.2910.15 3.9 100 10 3.4 0.55 45 0.160 0.19 2.4 70 11 4.5 0.35 38 0.248 0.212.5 85 Comparative 1 3.1 0.41 44 0.070 0.24 2.2 41 Example 2 2.0 0.63 350.062 0.18 1.9 35 3 1.9 0.61 48 0.063 0.18 1.8 32 4 15.1 0.12 63 0.3300.22 4.5 38 5 18.0 0.08 65 0.420 0.18 5.5 31 6 14.1 0.19 59 0.341 0.194.3 42

Example 12

250 g of Bofutsushosan Extract-F (manufactured by Alps PharmaceuticalIndustry Co., Ltd.), 500 g of Cellulose powder A, 220 g of spray driedlactose (SuperTab, manufactured by DMV-Fonterra Excipients GmbH & Co.KG), 30 g of pregelatinized starch “Swelstar” PD-1 (manufactured byAsahi Kasei Chemicals Corporation) were mixed in a plastic bag for 3minutes. 10 g of vegetable magnesium stearate (TAIHEI CHEMICALINDUSTRIAL CO., LTD.) was added to the mixture, and the obtained mixturewas further mixed in the plastic bag for 30 seconds. The mixture waspressed with a rotary presser (“Clean Press Correct 12HUK” (trade name),manufactured by Kikusui Seisakusho Ltd.). A tablet having a weight of200 mg, a diameter of 8 mm, and 12 R was prepared under a compressionforce of 5 kN with a gravity feeder at the number of rotations of theturn table of 54 rpm. The physical properties of the resulting tabletare shown in Table 2.

Examples 13 to 22

The operation was performed in the same manner as in Example 12 exceptthat the cellulose powder was changed to Cellulose powders B to K. Thephysical properties of the resulting tablets are shown in Table 2.

The cellulose powders according to the present invention providedtablets having a hardness of 40 N or more and a friability of 0.5% orless which are suitable for practical use. It turned out that thecellulose powders having an amount of organic carbon derived fromresidual impurities of 0.09 to 0.15% have an effect of enhancing anaroma and can suppress bad odors.

Comparative Examples 7 to 12

The operation was performed in the same manner as in Example 12 exceptthat the cellulose powder was changed to Cellulose powders L to Q. Thephysical properties of the resulting tablets are shown in Table 2.

The tablets in Comparative Examples had hardness and friability inferiorto those of the tablets containing the cellulose powder according to thepresent invention. The cellulose powders in Comparative Examples did notsuppress odors more significantly than the cellulose powder according tothe present invention did. Cellulose powders O to Q masked odors butonly weakened the odors probably because the amount of organic carbonderived from residual impurities was significantly larger. Accordingly,Cellulose powders O to Q had no effect of improving odors.

TABLE 2 Direct compressed tablet Amount of total organic carbon (%)derived from Swelling residual rate of impurities Tensile Odor tablet inCellulose Hardness strength Friability sensory diameter tablet powder(N) (MPa) (%) test (%) residues Example 12 A 85 2.6 0.19 4 1.5 0.144 13B 76 2.4 0.25 5 1.7 0.131 14 C 67 2.1 0.41 5 1.8 0.115 15 D 55 1.4 0.454 2.5 0.090 16 E 52 1.3 0.47 3 2.7 0.085 17 F 51 1.3 0.49 3 2 0.081 18 G92 2.9 0.11 3 1.2 0.152 19 H 100 3.1 0.08 3 0.9 0.164 20 I 125 3.9 0.042 0.7 0.292 21 J 74 2.3 0.31 3 1.6 0.159 22 K 90 2.8 0.15 2 1.3 0.248Comparative 7 L 39 1.2 0.65 3 3.4 0.068 Example 8 M 31 1.0 0.80 3 3.40.062 9 N 29 0.9 1.01 3 3.4 0.062 10 O 38 1.2 0.71 0 3.5 0.331 11 P 300.9 0.98 0 4.1 0.420 12 Q 35 1.1 0.62 0 3.5 0.340

Example 23

1120 g of Bofutsushosan Extract-F (manufactured by Alps PharmaceuticalIndustry Co., Ltd.), 400 g of Cellulose powder A, and 80 g of apregelatinized starch “Swelstar” PD-1 (manufactured by Asahi KaseiChemicals Corporation) were placed in a vertical granulator (VG-10,manufactured by Powrex Corporation). While the mixture was stirred(impeller: 280 rpm, cross screw: 3000 rpm), 200 g of an aqueous solutionof 6% HPC-L was added, and the mixture was kneaded for 3 minutes toprepare granules prepared by granulation. After the granules prepared bygranulation were dried, the granules were sieved with a 1410 μm sieve toprepare granules for pressing. 10 g of vegetable magnesium stearate(TAIHEI CHEMICAL INDUSTRIAL CO., LTD.) was added to 1000 g of thegranules for pressing, and was mixed therewith in a plastic bag for 30seconds. The mixture was pressed with a rotary presser (“Clean PressCorrect 12HUK” (trade name), manufactured by Kikusui Seisakusho Ltd.)(tableting pressure: 10 kN, weight: 380 mg, diameter: 9.5 mm, openfeeder, the number of rotations of the turn table: 54 rpm). The physicalproperties of the resulting tablet are shown in Table 3.

Examples 24 to 30

The same operation was performed as in Example 23 except that thecellulose powder was changed to Cellulose powders B to H, and the amountof the aqueous solution of 6% HPC-L was changed to 180 g in Cellulosepowder B, 170 g in Cellulose powder C, 120 g in Cellulose powder D, 120g in Cellulose powder E, 120 g in Cellulose powder F, and 200 g inCellulose powder G, and 220 g in Cellulose powder H. The physicalproperties of the resulting tablet are shown in Table 3.

Comparative Examples 13 to 15

The same operation was performed as in Example 23 except that thecellulose powder was changed to Cellulose powders L to N, and the amountof the aqueous solution of 6% HPC-L was changed to 170 g in Cellulosepowder L, 120 g in Cellulose powder M, 120 g in Cellulose powder N. Thephysical properties of the resulting tablets are shown in Table 3.

The tablets in Comparative Examples had hardness and friability inferiorto those of the tablets containing the cellulose powder according to thepresent invention. The cellulose powders in Comparative Examples did notsuppress odors more significantly than the cellulose powder according tothe present invention did. Cellulose powders G and H masked odors butonly weakened the odors probably because the amount of organic carbonderived from residual impurities was slightly larger. Accordingly,Cellulose powders G and H had no effect of improving odors.

TABLE 3 Tablet by wet granulation method Hard- Tensile Odor Celluloseness strength Friability sensory powder (N) (MPa) (%) test Example 23 A101 1.5 0.21 4 24 B 92 1.6 0.30 5 25 C 82 1.4 0.35 5 26 D 71 1.2 0.39 427 E 65 1.1 0.41 3 28 F 60 1.0 0.45 3 29 G 115 2.0 0.09 0 30 H 136 2.30.06 0 Comparative 13 L 48 0.8 0.54 3 Example 14 M 43 0.7 0.80 3 15 N 320.5 1.51 3

Example 31

A placebo tablet (microcrystalline cellulose/lactose=50/50, % by weight,diameter: 8 mm, 12 R, 200 mg tablet) was coated with 50% by weight ofsugar relative to the tablet. In the sugar coating, a spraying solutioncomposed of 780 g of talc (average particle size: 5 μm), 20 g of gumarabic, and 200 g of Cellulose powder A was used to form a sugar coatingfor spraying. While a pan was rotated, an aqueous solution of sucrosewas extended onto the placebo tablet. The spraying solution was thenadded, was extended, and was dried with about 60° C. hot air for 10minutes. This operation was repeated to form 50% by weight of sugarcoating layer relative to the placebo tablet. The physical properties ofthe resulting tablet are shown in Table 4.

Examples 32 to 38

The operation was performed in the same manner as in Example 31 exceptthat the cellulose powder was changed to Cellulose powders B to H. Thephysical properties of the resulting tablets are shown in Table 4.

Comparative Examples 16 to 18

The operation was performed in the same manner as in Example 31 exceptthat the cellulose powder was changed to Cellulose powders L to M. Thephysical properties of the resulting tablets are shown in Table 4.

Among the cellulose powders according to the present invention,Cellulose powders A to D having an amount of organic carbon derived fromresidual impurities of 0.09 to 0.15% had a whiteness of 95% or more andexcellent gloss.

TABLE 4 Sugar coated tablets Cellulose Whiteness powder (%) GlossExample 31 A 97 ◯ 32 B 96 ⊚ 33 C 96 ⊚ 34 D 95 ◯ 35 E 92 Δ 36 F 89 Δ 37 G93 Δ 38 H 92 Δ Comparative 16 L 92 Δ Example 17 M 90 Δ 18 N 91 Δ

INDUSTRIAL APPLICABILITY

In the cellulose powder according to the present invention, the amountof organic carbon derived from residual impurities extracted fromcellulose particles with hot water during hydrolysis is reduced, and theamount of organic carbon derived from impurities remaining inside thecellulose particles after drying is properly increased. As a result, thecellulose powder according to the present invention can improve not onlycompression compactibility but also flavor release from Kampo medicinesor the like and coloring properties of sugar coating layers.

The invention claimed is:
 1. A cellulose powder having an average degreeof polymerization of 100 to 350, a weight average particle size of frommore than 30 μm to 250 μm, an apparent specific volume of 2 to 15 cm³/g,and an amount of organic carbon derived from residual impurities of frommore than 0.07 to 0.291%, the amount of organic carbon derived fromresidual impurities being defined by the expression: amount of totalorganic carbon (TOC) in 5 g of a cellulose powder extracted from thecellulose powder (5 g) with an aqueous solution of 1% sodium hydroxide(80 mL)−amount of total organic carbon (TOC) in 5 g of a cellulosepowder extracted from the cellulose powder (5 g) with pure water (80mL), wherein a water absorption capacity of the cellulose powder is 1.8to 4.0 cm³/g.
 2. The cellulose powder according to claim 1, wherein theapparent specific volume is 2 to 6 cm³/g.
 3. The cellulose powderaccording to claim 1, wherein the apparent specific volume is from 2cm³/g to less than 4 cm³/g.
 4. The cellulose powder according to any oneof claims 1 to 3, wherein an intraparticle pore volume is from 0.1 cm³/gto less than 0.265 cm³/g.
 5. A molded article, comprising a cellulosepowder according to claim
 1. 6. The molded article according to claim 5,wherein the molded article contains one or more active ingredients.
 7. Amethod of preparing a cellulose powder, comprising: hydrolyzing anatural cellulose substance at a hydrochloric acid concentration of 0.05to 0.3% at a hydrolysis temperature of 80 to 150° C. for a hydrolysistime of 40 to 150 minutes to control a volume average particle size ofparticles in a cellulose dispersion liquid after the hydrolysis to be 70to 200 μm, and then spray drying the resulting dispersion liquid toprepare a cellulose powder having an average degree of polymerization of100 to 350, a weight average particle size of from more than 30 μm to250 μm, an apparent specific volume of 2 to 15 cm³/g, and an amount oforganic carbon derived from residual impurities of from more than 0.07to 0.291%, the amount of organic carbon derived from residual impuritiesbeing defined by the expression: amount of total organic carbon (TOC) in5 g of a cellulose powder extracted from the cellulose powder (5 g) withan aqueous solution of 1% sodium hydroxide (80 mL)−amount of totalorganic carbon (TOC) in 5 g of a cellulose powder extracted from thecellulose powder (5 g) with pure water (80 mL), wherein a waterabsorption capacity of the cellulose powder is 1.8 to 4.0 cm³/g.
 8. Themethod of preparing a cellulose powder of claim 7, wherein amount oforganic carbon derived from residual impurities is from more than 0.07to 0.115%.